心房颤动患者心房组织血管紧张素Ⅱ受体表达及血管紧张素转换酶抑制剂干预的初步研究

Regulation of angiotensin Ⅱ receptor subtypes during atrial fibrillation in humans and the effect of angiotensin-converting enzyme inhibitors

目的探讨心房颤动(房颤)患者心房组织血管紧张素Ⅱ(AngⅡ)受体基因转录和蛋白表达的变化以及血管紧张素转换酶抑制剂(ACEI)干预的影响。方法45例心脏外科手术患者,其中窦性心律和房颤患者各12例,应用低剂量ACEI的窦性心律和房颤患者分别为9例和12例。取右心耳组织通过逆转录聚合酶链反应和免疫组织化学技术测量血管紧张素Ⅱ1型受体(AT1)和血管紧张素Ⅱ2型受体(AT2)mRNA和蛋白的相对表达量。结果窦性心律和房颤患者之间的心房组织AT1和AT2mRNA表达量差异无统计学意义;房颤患者心房组织AT1蛋白表达量明显低于窦性心律患者(2.63±1.00vs4.64±1.48,P<0.001),AT2蛋白表达量明显高于窦性心律患者(6.20±2.17vs3.72±0.88,P<0.05);应用低剂量ACEI的窦性心律和房颤患者分别与未应用ACEI的窦性心律和房颤患者相比,AT1和AT2的mRNA和蛋白表达量差异无统计学意义。结论房颤时AT1蛋白表达下调,AT2蛋白表达上调,相应的mRNA表达水平差异无统计学意义,提示肾素血管紧张素系统参与了房颤的心房结构重构;低剂量ACEI不能逆转房颤AngⅡ受体重构。

Objective To determine the atrial expression of angiotensin Ⅱ type 1 and type 2 receptors (AT_1 and AT_2) in patients with atrial fibrillation (AF) and the effect of angiotensin-converting enzyme inhibitors (ACEI).Methods Atrial tissue samples from 45 patients undenwent open heart surgery were examined.Of which,12 patients were in AF,and 12 patients in sinus rhythm(SR).Low dose ACEI was administrated in 12 patients with AF and 9 patients with SR.AT_1 and AT_2 were semi-quantified at the mRNA and protein level by reverse transcription-polymerase chain reaction and immunohistochemistry.Results Both the expression of AT_1 and AT_2 both at mRNA level were similar in patients with AF compared with patients with SR,respectively.The expression of AT_1 at protein level was significantly decreased in patients with AF compared with patients with SR (2.63±1.00 vs 4.64±1.48,P<0.001).In contrast,the expression of AT_2 at protein level was significantly increased in patients with AF compared with patients with SR (6.20±2.17 vs 3.72±0.88,P<0.05).Administration of low dose ACEI had no effect on the expression of AT_1 and AT_2 both at mRNA and protein level.Conclusion AF is associated with the down-regulation of atrial AT_1 and up-regulation of AT_2 proteins.These findings may help define the pathophysiological role of rennin-angiotensin system in the structural remodeling of the fibrillation atria.Administration of ACEI in low dose can not reverse the receptor remodeling of angiotensin Ⅱ during AF.